Cell apoptosis is an autonomic ordered programmed cell death controlled by genes in order to maintain homeostasis which plays an important role in organism evolution, homeostasis and multi-system development. Cell apoptosis signal transduction is divided into internal (mediated by interaction between death receptor and ligand) and exterior (mediated by cell stress and mitochondria permeability) transduction and these two transduction converge on Caspase. Once apoptosis signal is activated, Caspase will dissociate lots of substrates associated with cell death which causes cells die.
Inhibitor of apoptosis proteins (IAPB) is a family of highly conserved endogenous anti-apoptosis factors which suppresses apoptosis through inhibiting Caspase activation and participating in mediating nuclear factor NF-κB. Roy et al. found IAP was a neuronal apoptosis inhibitor protein (NAIP) in research of spinal muscular atrophy firstly in 1995. Subsequently, cellular inhibitor of apoptosis protein (cellular TAP, c-IAP1 and c-IAP2), X chromosome linked inhibitory of apoptosis factor(XIAP), Survivin, melanoma inhibitor of apoptosis protein (melanoma-TAP, ML-IAP/Livin), testi-specific inhibitor of apoptosis protein (hILP) and BIR repeat containing ubiquitin-conjugating enzyme, and eight human IAPB family protein members has been found so far. Among these eight IAP family, cIAP1, cIAP2, XIAP were sufficiently studied. They contain three structural functional domains, named BIR1, BIR2 and BIR3, which play roles in apoptosis suppression through inhibiting Caspase 3, 7, 9 and so on.
Smac, fully named second mitochondria-derived activator of caspases, is a protein mediating cellular apoptosis in mitochondrial which promotes apoptosis through reversing inhibitor of apoptosis proteins (IAPs), particular X chromosome linked inhibitory of apoptosis factor (XIAP). When cells are activated by apoptosis, mitochondrial releases Smac into cytoplasm, which binds to IAPs and results in IAPB losing suppression on caspase and promoting cellular apoptosis. Smac binds to multi-IAPB directly with tetrapeptide in N-terminus which blocks IAPs' roles in apoptosis suppression and promoting cellular apoptosis effectively. Various IAP inhibitors, also named Smac mimetics were reported by lots of references which inhibited proliferation of cancer cells and promoted apoptosis of infected cells in vivo and in vitro. Among them, Birinapant, LCL-161, AT-406 and so on have entered into clinical phase I or phase II. However, novel IAP antagonists with better activity, selectivity and safety are still in a huge demand.

Background information referred to references below:
Nat.rev.Drug Discov.2012, 11, p 109-124; Pharmacology & Therapeutics, 2014, 144, p 82-95; J.Med.Chen.2014, 57, p 3666-3677; Proc.Natl.Sci.Acad.USA2015, 112, p 5759-5802; CONDON, Stephen, M. etc, WO/2006/091972.